Leprosy Mailing List – July 2, 2024
Ref.: (LML) Single dose rifampicin prophylaxis in three Brazilian states
From: Joel Almeida, Mumbai, India
Dear Pieter and colleagues,
Why did Brazil reject SDR PEP? Were they wrong? Brazilian authorities keep track of what happens to their people, and report it well. What was observed? Was SDR PEP beneficial or harmful?
From about 2016 to about 2018 SDR PEP (single dose rifampicin post-exposure prophylaxis variously labelled LPEP or PEP HANS etc) with BCG was implemented in parts of three states of Brazil: Mato Grosso, Tocantins and Pernambuco. SDR PEP was given to household contacts, neighbours and social contacts of newly diagnosed patients. Neighbouring states did not have SDR PEP. These were Rondonia near Mato Grosso, Maranhão near Tocantins and Bahia near Pernambuco. The latter three states therefore can serve as non-PEP comparators.
Official Brazilian reports monitor and report on program activities and outcomes.(1) What happened after SDR PEP was introduced?
Multibacillary (MB) HD (leprosy) increased dramatically in the SDR PEP states over time as well as compared to the non-PEP neighbour states.
Visible deformity (grade 2 disability) among newly diagnosed HD patients increased dramatically in the SDR PEP states over time as well as compared to the non-PEP neighbour states.
Does such rapid emergence of differences in outcome between SDR PEP and non PEP states have any precedent? Are there any relevant randomised clinical trials?
A cluster randomised controlled trial in Bangladesh measured the effect of SDR PEP on the incidence rate among household contacts and close neighbours of newly diagnosed HD patients.(2) All the included contacts received BCG. 8 to 12 weeks later, a randomly allocated half of these contacts, in clusters, received SDR PEP. The control group consisted of those who did not receive SDR PEP. The outcome specified in the protocol (3) was clinical HD detected among contacts within the first 2 years. The type of HD (MB or PB, paucibacillary) developed by contacts was noted.
In that randomised controlled trial in Bangladesh, over three times as many new MB HD cases arose in the SDR PEP group as in the control group (without SDR PEP). Notably, the excess of new MB HD in the SDR PEP group increased between year 1 and year 2. The protocol (3) did not extend beyond 2 years after administration of SDR PEP.
In Brazil too the excess of MB HD occurred within two years of giving SDR PEP.
It is concluded that in the three Brazilian states SDR PEP was an important factor in the increased risk of new MB HD observable within two years of introducing SDR PEP. It is not possible to exclude SDR PEP and the consequent increase in risk of new MB HD as an important factor in the observed boost in reported visible deformity in the SDR PEP states.
Discussion
The visible deformities of HD tend to be irreversible. The people most likely to suffer such deformities tend to be on low and uncertain incomes to begin with. Such uncertainty of income can ripen into full-blown destitution once visible deformity sets in. The Bangladesh RCT did not report the occurrence of visible deformity. The Brazilian program duly does.
The socio-economic impacts of SDR PEP depend on the viewpoint adopted. To a person suffering permanent deformity, the socio-economic impact is less favourable than in the case of the organisations that secure funding to promote SDR PEP.
Mathematical models are sometimes used in attempts to condone or explain away inconvenient observations following SDR PEP. No mathematical model can restore permanently damaged limbs or eyes.
The serious harms that unexpectedly accompany SDR PEP in an endemic area, observed even in the Bangladesh RCT, are unnecessary for the purpose of HD control. The WHO 2018 guidelines had only conditionally recommended SDR PEP. The guidelines have an Annex 1 disclosing conflicts of interest among esteemed external reviewers.(4) Would it be a bad idea henceforth to exclude all financial conflicts of interest while developing or reviewing guidelines?
What information is needed for informed consent in the light of evidenced harm?
Is it necessary to raise funds by harming people in endemic countries? Organisations such as LEPRA seem to raise funds without reliance on promoting SDR PEP.
Were our Brazilian colleagues wrong to resist external pressures to reintroduce SDR PEP?
Joel Almeida.
Reference
1. Secretaria de Vigilância em Saúde, Ministério da Saúde (Brasil). Hanseníase | 2023. Boletim Epidemiológico. Número Especial | Jan. 2023
2. Richardus R, Alam K, Kundu K et al. Effectiveness of single-dose rifampicin after BCG vaccination to prevent leprosy in close contacts of patients with newly diagnosed leprosy: A cluster randomized controlled trial. International Journal of Infectious Diseases 88 (2019) 65–72.
3. Richardus RA, Alam K, Pahan D et al. The combined effect of chemoprophylaxis with single dose rifampicin and immunoprophylaxis with BCG to prevent leprosy in contacts of newly diagnosed leprosy cases: a cluster randomized controlled trial (MALTALEP study). BMC Infect Dis. 2013 Oct 3;13:456. doi: 10.1186/1471-2334-13-456.
4. WHO. Guidelines for the Diagnosis, Treatment and Prevention of Leprosy. 2018
LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << editorlml@gmail.com
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